tbuckley/cabot-search huggingface dataset:
435 Burden of disease and unmet needs in the diagnosis and management of atopic dermatitis in the Middle East
Authors: Omar Mahmoud, Enas Attia, Gil Yosipovitch
Journal: British Journal of Dermatology (2023)

Abstract Atopic dermatitis (AD) affects diverse ethnic groups with significant disparities in prevalence, disease progression, clinical outcomes and access to care. There are limited data on AD in the Middle East, yet there is a substantial economic and psychosocial burden of AD in this region with a large unmet need with regards to disease management that is critical to address. There is a trend of increasing prevalence of AD in the Middle East; however, due to the large environmental, socioeconomic, and sociocultural heterogeneity of this region, prevalence varies greatly across and within countries. Similarly, clinical differences in disease presentations exist across the Middle East, although regional data ared limited. We will present clinical phenotypes of AD common in different regions of the Middle East, data on prevalence, genetic variations and challenges of treatment. Further studies exploring molecular biomarkers, genetic polymorphisms, immune factors and the microbiome of patients in the Middle East will help to elucidate the mechanism behind ethnic differences in AD in this population as well as to help understand treatment response and susceptibilities.
389 A CME virtual patient simulation activity evaluated the management of adults with atopic dermatitis
Authors: Shari J Dermer, Briana Betz, Elaine Bell, Philippe  Guedj, Piyali Chatterjee-Shin
Journal: British Journal of Dermatology (2023)

Abstract Atopic dermatitis (AD) is an inflammatory skin disease with significant burden for patients. Individuals with moderate to severe AD frequently require treatment with systemic agents; however, this does not necessarily occur in clinical practice. This study was intended to evaluate the effect of online virtual patient simulation (VPS)-based CME in improving the management of moderate to severe AD. The educational intervention was designed to close gaps related to (i) underrecognition and undertreatment of patients with AD who would benefit from systemic agents and (ii) improve adoption of new therapies for moderate to severe AD. Case-based interventions in an online VPS platform allowed learners to interview patients via video, order tests, make diagnoses and order treatments supported by an extensive database matching the scope and depth of actual practice. Clinical decisions were analysed, and learners received immediate feedback in a short-form clinical guidance (CG) based on current evidence. Learners were permitted to modify their decisions post-CG. Pre- to post-CG decisions were compared using a McNemar’s test with P &amp;lt; 0.05 as significant. The intervention launched on March 4, 2022, and data were collected through June 2022. We report on data from n = 188 dermatologists and n = 130 allergists who participated in two virtual cases. Significant performance-based improvements were made in Case 1 and Case 2 as a result of education (%pre vs. %post, Case1 and %pre vs. %post, Case2). Assessing appropriateness of systemic AD therapy: ordering evaluation of itch with the NRS (61% vs. 71% and 58% vs. 68%); assessing BSA affected (70% vs. 78% and 70% to 80%); evaluating IGA (39% vs. 54% and 65% vs. 70% [ns]); and asking about itch, sleep and ability to function in daily activities (88% vs. 92% and 91% vs. 99%).Diagnosing moderate to severe AD: 47% vs. 58% and 54% vs. 62%.Selecting an evidence-based AD treatment: start FDA-approved IL-4 receptor blocker (18% vs. 47% and 23% vs. 35%); other treatment choices were topical corticosteroids, topical calcineurin inhibitors, crisaborole, systemic immunosuppressants, systemic steroids, JAK inhibitors (upadacitinib and abrocitinib) and tralokinumab. This study demonstrated that immediate feedback provided in short-form clinical guidance in a VPS that immerses and engages specialists in an authentic and practical learning experience resulted in changes in performance relating to assessing and treating virtual patients with moderate to severe AD. This initiative also revealed gaps in diagnosing moderate to severe AD, and in selecting evidence-based, FDA-approved systemic treatments. Future education is needed to close these gaps.
440 Prevalence and burden of rhinoconjunctivitis in atopic dermatitis patients: a cross-sectional study
Authors: Isaac Betaharon, Jonathan I Silverberg
Journal: British Journal of Dermatology (2023)

Abstract Allergic rhinoconjuncitivitis can be highly symptomatic and burdensome and complicates the management of eyelid and facial dermatitis in persons with atopic dermatitis (AD). However, little is known about the prevalence, burden and predictors of allergic rhinoconjunctivitis symptoms in patients with AD, particularly among adults. This study aims to determine the prevalence and predictors of allergic rhinoconjunctivitis severity in patients with AD. A cross-sectional, dermatology practice-based study was performed at an urban academic medical center (n = 507). Atopic dermatitis severity was assessed by investigator-assessed Eczema Area and Severity Index (EASI), body surface area (BSA), investigator’s global assessment (IGA), objective-SCORing AD and patient-reported Global Assessment (PtGA). Impact of allergic rhinoconjunctivitis symptoms was assessed by Rhinoconjunctivitis Quality of Life Questionnaire. The cohort included children (&amp;lt;18 years; n = 36, 7.1%), young adults (18–49 years; n = 281, 55.4%) and older adults (≥50 years; n = 190, 37.5%), males (n = 219, 43.2%) and females (n = 288, 56.8%), Hispanics (n = 43, 8.5%), Blacks (n = 50, 9.9%), White non-Hispanics (n = 349, 68.8%), Asians (n = 51, 10.1%) and multiracial/other race (n = 14, 2.8%); 413 (81.5%) had private insurance. Overall, 246 (48.5%) reported a history of hay fever, and 15 (3.0%) and 416 (82.1%) of patients with AD reported having trouble with one or multiple rhinoconjunctivitis symptoms in the past 2 weeks; 30 (5.9%) and 365 (72.0%) of patients with AD had quite a bit or extreme trouble with one or multiple rhinoconjunctivitis symptoms, respectively. More severe AD overall (EASI, BSA, IGA and PtGA), as well as more severe facial dermatitis, flexural eczema and xerosis were associated with worse rhinoconjunctivitis symptoms, whereas, race, gender and presence of nummular dermatitis were generally not associated with rhinoconjunctivitis symptom severity. Quite a bit or extreme trouble from one or more rhinoconjunctivitis symptoms was reported in 39 (56.5%) patients with clear/almost clear, 85 (74.6%) mild, 135 (82.8%) moderate and 106 (84.8%) severe PtGA scores. In multivariable ordinal logistic regression models that controlled for demographics, AD severity was significantly associated with higher odds of a wide range of nasal and ocular symptoms, as well as rhinoconjunctivitis symptoms negatively impacting daily activities, causing sleep and practical problems, and negative emotions. Allergic rhinoconjunctivitis symptoms occurred in more than 4 out of 5 patients with AD overall, and almost 90% of patients with severe AD. Allergic rhinoconjunctivitis was more common in those with more severe AD, and particularly those with more severe facial dermatitis, flexural eczema and xerosis. Rhinconjunctivitis symptoms negatively impact the lives of patients with AD and warrant appropriate screening and management in clinical practice.
437 Treatment-emergent adverse events in patients aged 6 months to 5 years with moderate-to-severe atopic dermatitis treated with dupilumab in an open-label extension clinical trial
Authors: Amy S Paller, Elaine C Siegfried, Robert  Sidbury, Benjamin Lockshin, Michael  Cork, Andreas Pinter, Jing Xiao, Faisal A Khokhar, Ashish Bansal, Randy  Prescilla
Journal: British Journal of Dermatology (2023)

Abstract Atopic dermatitis (AD) is a chronic systemic inflammatory disease requiring long-term management. However, availability of long-term AD treatments with an acceptable risk-benefit profile is limited in pediatric patients. This ongoing phase 3 open-label extension (OLE; NCT02612454) enrolled patients aged 6 months to 17 years with moderate-to-severe AD. Patients were treated with dupilumab (weight-based dosing): 200 mg every 4 weeks (q4w; 5–14 kg), 300 mg q4w (15–29 kg) and 200 mg q2w (30–59 kg). Here we report safety data (cutoff date July 31, 2021) for 180 patients aged 6 months to 5 years who enrolled in the OLE. Of the 180 patients reported, 122 (67.8%) completed up to 16 weeks of the study, 30 (16.7%) up to Week 52 and 15 (8.3%) up to Week 156. A total of 167 (92.8%) patients were continuing treatment at the time of data cutoff. At baseline, the mean (SD) age was 3.9 (1.3) years. One hundred and nine (60.6%) patients reported treatment-emergent adverse events (TEAEs); the most common were nasopharyngitis (12.8%), upper respiratory tract infection (11.7%) and pyrexia (11.7%). One (0.6%) patient had a treatment-related severe TEAE (urticaria) that led to study drug discontinuation. Two (1.1%) patients had serious TEAEs (anaphylactic reaction and pneumonia mycoplasmal) of severe and moderate intensity, respectively. Both serious TEAEs were unrelated to treatment. Long-term safety of dupilumab in this pediatric population was generally consistent with the known dupilumab safety profile in adults and older pediatric patients.
402 Efficacy of lebrikizumab in adolescent patients with moderate-to-severe atopic dermatitis: 16-week results from three randomized phase 3 clinical trials
Authors: Adelaide Hebert, Carsten Flohr, H Chih-ho Hong, Alan Irvine, Evangeline  Pierce, Hany  Elmaraghy, Wen Xu, Sreekumar  Pillai, Zach Dawson, Elaine Siegfried, Stephan  Weidinger
Journal: British Journal of Dermatology (2023)

Abstract Lebrikizumab, a high-affinity monoclonal antibody targeting IL-13, previously demonstrated clinical efficacy in adults and adolescents with atopic dermatitis (AD) in phase 3 trials. Here we evaluate 16-week efficacy outcomes of lebrikizumab in adolescent patients with moderate-to-severe AD from 3 randomized, double-blind, placebo-controlled phase 3 trials: ADvocate1, ADvocate2 and ADhere. Eligible adolescents (≥12 to &amp;lt;18 years weighing ≥40 kg) were randomized 2 : 1 to subcutaneous lebrikizumab (loading doses of 500 mg at Baseline and Week 2 followed by 250 mg every 2 weeks) or placebo in ADvocate1&amp;2 as monotherapy, and in combination with topical corticosteroids (TCS) in ADhere. Efficacy analyses at Week 16 included IGA (0,1) with ≥2-point improvement, EASI-75, and Pruritus NRS ≥4-point improvement. Adolescent data from ADvocate1 and ADvocate2 were pooled, and ADhere data were analysed separately. ADvocate2 and ADhere analyses were performed on a modified population, excluding 10 adolescent patients from a single site whose eligibility could not be confirmed. Combined adolescent 16-week results from ADvocate1 and ADvocate2 [lebrikizumab (n = 67) vs. placebo (n = 35)] were IGA (0,1) with ≥2-point improvement from baseline 46.6% vs. 14.3% (P &amp;lt; 0.01), EASI-75 62.0% vs. 17.3% (P &amp;lt; 0.001) and Pruritus NRS ≥4-point improvement from baseline 48.9% vs. 13.1% (P &amp;lt; 0.01), respectively. The corresponding proportions in ADhere (lebrikizumab + TCS, n = 32; placebo + TCS, n = 14) were IGA (0,1) 57.3% vs. 28.6% (P = 0.071), EASI-75 88.0% vs. 57.1%, (P &amp;lt; 0.05) and Pruritus NRS 45.8% vs. 13.8%, (P = 0.078), respectively. Lebrikizumab treatment with or without TCS demonstrated clinical efficacy in adolescents with moderate-to-severe AD.
426 Efficacy and safety of abrocitinib in adolescents with moderate-to-severe atopic dermatitis from the JADE clinical trial program
Authors: Lawrence F Eichenfield, Carsten Flohr, Christine  Bangert, Alan D Irvine, Stephan  Weidinger, John Nesnas, Herwig  Koppensteiner, Fan Zhang, Ricardo Rojo, Gary Chan
Journal: British Journal of Dermatology (2023)

Abstract Once-daily oral abrocitinib, a Janus kinase 1-selective inhibitor, was effective and well tolerated as a monotherapy in adult and adolescent patients with moderate-to-severe atopic dermatitis (AD), as well as in combination with medicated topical therapy in adolescents with moderate-to-severe AD. This study aims to investigate efficacy and safety of abrocitinib in adolescents with moderate-to-severe AD from the JADE clinical trial program. Patients aged 12–17 years with moderate-to-severe AD and an inadequate response to ≥4 consecutive weeks of topical medication or treatment with systemic therapy for AD, both within the past 6 months, were randomly assigned [2:2:1 JADE MONO-1/MONO-2 (NCT03349060/NCT03575871); 1:1:1 JADE TEEN (NCT03796676)] to receive once-daily oral abrocitinib (200 or 100 mg) or placebo as monotherapy (JADE MONO-1 and JADE MONO-2) or in combination with medicated topical therapy (JADE TEEN) for 12 weeks. Coprimary endpoints were proportion of patients achieving Investigator’s Global Assessment (IGA) response [clear (0) or almost clear (1) with ≥2-grade improvement from baseline] and proportion of patients who achieved ≥75% improvement in Eczema Area and Severity Index score (EASI-75) at Week 12. A key secondary endpoint was the proportion of patients achieving ≥4-point improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4; used with permission from Regeneron Pharmaceuticals and Sanofi) at Week 12. Drug safety was also assessed. Overall, 285 and 124 adolescents in JADE TEEN and JADE MONO-1/MONO-2, respectively, were treated. In JADE TEEN, more abrocitinib-treated (200 mg, 100 mg) than placebo-treated patients achieved IGA (46.2%, 41.6% vs. 24.5%; P &amp;lt; 0.05 for both doses), EASI-75 (72.0%, 68.5% vs. 41.5%; P &amp;lt; 0.05 for both doses) and PP-NRS4 (55.4%, 52.6% vs. 29.8%; P &amp;lt; 0.01 for 200 mg vs. placebo) responses at Week 12. Adverse events (AEs) were reported for 62.8%, 56.8% and 52.1% of patients in 200 mg, 100 mg and placebo groups, respectively; 1 (1.1%), 0 and 2 patients (2.1%) had serious AEs. JADE MONO-1/MONO-2 safety results were similar, but efficacy results were lower, as expected for monotherapies. Results from JADE clinical trials suggest that abrocitinib was effective in adolescents with moderate-to-severe AD, with an acceptable safety profile.
413 Improvement in itch, symptoms and quality of life with upadacitinib through week 16 in adults and adolescents with atopic dermatitis: results from phase 3 studies (Measure Up 1, Measure Up 2 and AD Up)
Authors: Peter Lio, Lawrence F Eichenfield, Danielle  Marcoux, Wan-Ju Lee, Henrique D   Teixeira, Eliza M Raymundo, Amy E  Gamelli, Ayman Grada, Xiaofei Hu, Alan D Irvine
Journal: British Journal of Dermatology (2023)

Abstract Atopic dermatitis (AD) is characterized by intense itch and symptoms that adversely impact quality of life (QoL). Upadacitinib is a selective Janus kinase-1 inhibitor approved for moderate-to-severe AD. We assessed the effect of once daily oral upadacitinib (15 or 30 mg), with or without concurrent topical corticosteroid treatment, on patient-reported outcomes for adults and adolescents with moderate-to-severe atopic dermatitis during the double-blind, placebo-controlled phase 3 clinical trials, Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422) and AD Up (NCT03568318). Assessments included itch (Worst Pruritus Numerical Rating Scale), skin pain and symptom severity (AD Symptom Scale), symptom frequency (Patient Oriented Eczema Measure) and sleep, daily activities and emotional state (AD Impact Scale). Post hoc analysis of 2240 adults and 344 adolescents randomized patients was performed. By Week 2, more patients receiving upadacitinib achieved a clinically relevant response in itch, skin pain, symptom severity, symptom frequency, sleep, daily activities and emotional state vs. placebo across studies among adults (upadacitinib 15 mg: 30.8–87.3%; upadacitinib 30 mg: 38.0–89.9%; placebo: 2.1–43.1%; nominal P &amp;lt; 0.001 for all comparisons) and adolescents (upadacitinib 15 mg: 19.4–82.9%; upadacitinib 30 mg: 35.3–97.6%; placebo: 0–41.0%; nominal P &amp;lt; 0.05 for 37/42 comparisons). These trends continued through week 16 where response rates for all outcomes improved with upadacitinib vs. placebo in adults (upadacitinib 15 mg: 42.9–80.4%; upadacitinib 30 mg: 60.9–84.6%; placebo: 10.1–38.1%; nominal P &amp;lt; 0.001 for all comparisons) and adolescents (upadacitinib 15 mg: 33.3–78.0%; upadacitinib 30 mg: 50.0–85.7%; placebo: 2.8–43.6%; nominal P &amp;lt; 0.05 for 41/42 comparisons). These findings highlight the rapid, sustained efficacy of once daily oral upadacitinib in improving symptom burden and QoL in adults and adolescents with moderate-to-severe AD.
410 Dupilumab treatment reduces total IgE levels in patients 6 months and older with moderate-to-severe atopic dermatitis
Authors: Elaine C Siegfried, Michael J Cork, Mark  Boguniewicz, Mette Deleuran, Eric L   Simpson, Zhen Chen, Drew Clearfield, Parul Shah, Ainara Rodríguez Marco
Journal: British Journal of Dermatology (2023)

Abstract Atopic dermatitis (AD) is a type 2 inflammatory disease characterized by elevations in several biomarkers including serum IgE—a key downstream mediator in the type 2 adaptive immune response. Patients with moderate-to-severe AD were enrolled for 16 weeks in any of six randomized, placebo-controlled, phase 3 studies: in LIBERTY AD PRESCHOOL, (NCT03346434 part B) patients aged 6 months to 5 years were treated with dupilumab 200/300 mg every 4 weeks (q4w) + topical corticosteroids (TCS; n = 83) or placebo + TCS (n = 79); in LIBERTY AD PEDS (NCT03345914), patients aged 6–11 years were treated with dupilumab + TCS [100/200 mg q2w (n = 122), 300 mg q4w (n = 122)] or placebo + TCS (n = 123); in LIBERTY AD ADOL (NCT03054428), patients aged 12–17 years were treated with dupilumab [200/300 mg q2w (n = 82), 300 mg q4w (n = 83)] or placebo (n = 85); and in LIBERTY AD CHRONOS/SOLO1/SOLO2 (NCT02260986/NCT02277743/NCT02277769, pooled), patients aged ≥18 years were treated with dupilumab [300 mg q2w (n = 563),300 mg qw (n = 781) ] or placebo (n = 775). The TCS were allowed in CHRONOS only. At Week 16, dupilumab treatment significantly (P &amp;lt; 0.0001) reduced median total serum IgE levels [kU/L (IQR)] compared with placebo in patients aged 6 months to 5 years [843 (207–3300) vs. 3625 (540.5–8585)], 6–11 years [1519 (532–3808) vs. 3862 (1166–9999)], 12–17 years [1391 (436–2842) vs. 4569 (800.5–10000)] and ≥18 years [1340 (229–4360) vs. 3722 (555–10000)]. Dupilumab treatment reduced total serum IgE levels in patients aged 6 months and older with moderate-to-severe AD. Overall safety was consistent with the known dupilumab safety profile.
414 Baseline serum biomarkers do not predict dupilumab treatment response in adults with moderate-to-severe atopic dermatitis
Authors: Stephan Weidinger, Lisa A Beck, Marjolein S   de Bruin-Weller, Jacob P Thyssen, Kenji  Kabashima, Emma Guttman-Yassky, Cezmi A Akdis, Zhen Chen, Noah A Levit, Mike Bastian
Journal: British Journal of Dermatology (2023)

Abstract Previous analyses based on short-term, phase 2 studies reported that baseline biomarkers do not correlate with clinical outcomes following dupilumab treatment in patients with atopic dermatitis (AD). This new analysis based on 16-week, phase 3 studies reports whether pretreatment levels of common serum biomarkers can predict treatment response to dupilumab in adults with moderate-to-severe AD. LIBERTY AD SOLO 1 and 2 (NCT02277743 and NCT02277769), two randomized, double-blind studies, included patients ≥18 years-old with moderate-to-severe AD treated with dupilumab 300 mg every 2 weeks or placebo for 16 weeks. Correlation between change in Eczema Area and Severity Index (EASI) and log of baseline IgE, CC chemokine ligand 17 [CCL17; previously referred to as thymus and activation-regulated chemokine (TARC)] and lactate dehydrogenase (LDH) at baseline was assessed using Spearman’s correlation coefficient (ρ). At Week 16, change in EASI showed little correlation with baseline total IgE [Spearman’s correlation coefficient (ρ) = –0.14, n = 370 for dupilumab; ρ = –0.03, n = 202 for placebo], baseline CCL17 (ρ = –0.28, n = 369 for dupilumab; ρ = –0.05, n = 201 for placebo) or baseline LDH (ρ = –0.30, n = 370 for dupilumab; ρ = –0.08, n = 202 for placebo). Overall safety was consistent with the known dupilumab safety profile. Baseline levels of total IgE, CCL17 and LDH do not predict treatment response to dupilumab, as measured by EASI, in adults with moderate-to-severe AD.
392 Safety of amlitelimab in a Phase 2a clinical trial of patients with moderate-to-severe atopic dermatitis
Authors: Stephan Weidinger, Michael Cork, Adam Reich, Thomas Bieber, Sally Gilbert, Sonia Quaratino, Rosamund Wilson, Ben Porter-Brown
Journal: British Journal of Dermatology (2023)

Abstract Amlitelimab (SAR445229), a fully human, nondepleting, noncytotoxic, monoclonal antibody, binds to OX40Ligand (OX40L) on antigen-presenting cells to block OX40-OX40L interactions. Outcomes from a 36-week, double-blind, Phase 2a trial (NCT03754309) in patients with moderate-to-severe atopic dermatitis are described. This study aims to assess the safety of OX40-OX40L signaling blockade with amlitelimab in patients with moderate-to-severe atopic dermatitis. Eighty-nine patients were randomized to amlitelimab low-dose (LD; 200-mg loading/100-mg maintenance Q4W), high-dose (HD; 500 mg/250 mg Q4W) or placebo. The coprimary safety endpoint was treatment-emergent adverse event (TEAE) incidence to W16. Safety was assessed to W36. Amlitelimab was well tolerated. Related TEAE incidence was similar between amlitelimab [LD 35% (10/29); HD 20% (6/30)] and placebo [31% (9/29)] to W16 and W36 [LD 10% (2/20); HD 0 (0/22); placebo 0 (0/17)]. The TEAEs more common with amlitelimab vs. placebo (≥5% difference) to W16 included headache [LD 0; HD 3 (10%); placebo 1 (3.4%)], upper respiratory tract infection [3 (10.3%); 0; 1 (3.4%)], hyperhidrosis [0; 2 (6.7%); 0], pyrexia [2 (6.9%); 0; 0], aspartate aminotransferase increased [0; 2 (6.7%); 0] and iron-deficiency anemia [2 (6.9%); 0; 0]; and to W36, Herpes simplex [0; 2 (9.1%); 0]. Before W16, one severe adverse event (SAE) of infected dermal cyst was reported as possibly related; it resolved, and the patient completed the study. Post-W16, one unrelated SAE of sudden death occurred 87 days following the final amlitelimab dose. No hypersensitivity or tolerability events, or clinically meaningful changes in laboratory values, vital signs or electrocardiogram recordings were reported. Amlitelimab was well tolerated in a Phase 2a trial of patients with moderate-to-severe atopic dermatitis, confirming the unremarkable safety profile observed in Phase 1.